Water → 2-(1,6-dimethyl-1H-indazol-3-yl)-N-(1-(hydroxymethyl)cyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246680ノート

反応式

HRID 246680 の反応式
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:11])[CH:9]=2)[C:4]([C:12]2[N:17]=[C:16]3[C:18]([C:21](O)=[O:22])=[CH:19][NH:20][C:15]3=[N:14][CH:13]=2)=[N:3]1.[NH2:24][C:25]1([CH2:28][OH:29])[CH2:27][CH2:26]1.CCN=C=NCCCN(C)C.O>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:11])[CH:9]=2)[C:4]([C:12]2[N:17]=[C:16]3[C:18]([C:21]([NH:24][C:25]4([CH2:28][OH:29])[CH2:27][CH2:26]4)=[O:22])=[CH:19][NH:20][C:15]3=[N:14][CH:13]=2)=[N:3]1

参加物

7

反応物 4

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 14146220(1-Aminocyclopropyl)methanolHCID 712798782-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid

生成物 1

HCID 712796902-(1,6-dimethyl-1H-indazol-3-yl)-N-(1-(hydroxymethyl)cyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide収率 36%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

To a stirred mixture of 2-(1,6-dimethyl-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (80 mg, 0.26 mmol) and (1-aminocyclopropyl)methanol (34 mg, 0.39 mmol) in DMF (3 mL), was added EDCI (100 mg, 0.52 mmol) followed by DMAP (63 mg, 0.52 mmol). The mixture was stirred at room temperature for 16 hours. Then the mixture was poured into water (5 mL) and filtered. The crude product was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 45% acetonitrile/55% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(1,6-dimethyl-1H-indazol-3-yl)-N-(1-(hydroxymethyl)cyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (35 mg, 36%) as a white solid. MS: (M+H)+=377; 1H NMR (300 MHz, DMSO): δ 13.84 (s, 1H), 9.12 (s, 1H), 8.74 (s, 1H), 8.43-8.40 (m, 2H), 7.56 (s, 1H), 7.21 (d, 1H, J=8.4 Hz), 4.89 (brs, 1H), 4.16 (s, 3H), 3.62 (s, 2H), 2.55 (s, 3H), 0.97-0.86 (m, 4H).

後処理

  1. filtrationfiltered
  2. customThe crude product was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  3. wait35% acetonitrile/65% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 45% acetonitrile/55% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

出典と根拠

ORDレコード
ord-18de31069f6f425a9010c24e58d5ae1d
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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